During the last year we synthesized four different types of heparin-linked agarose and found that they preferentially adsorb thrombin, antithrombin III (heparin cofactor), factor IX and factor XI. In the coming year, experiments will be conducted to utilize these adsorbants for the purification of the above mentioned plasma components. Advantage will be taken of the specificity of the heparin-agarose and the individual binding and elution properties of the clotting factors. It is expected that results of these studies will provide purified materials for possible clinical applications and for further investigations of coagulation mechanisms. Studies will also be continued on the effect of modification of specific groups of heparin (e.g., carboxyl, sulfate) on its anticoagulant activity. This research will be extended to experiments with purified coagulation components which are inhibited by heparin. Thus, investigations will be made on the effectiveness of the heparin derivatives to inhibit thrombin, factor X and factor XI in the presence and absence of antithrombin III. Similar studies are also planned with factor VII and factor IX. These and analogous investigations should define the mechanism of action of heparin and should also clarify certain aspects of the coagulation process.